Human disease is a consequence of both genetic susceptibility and environmental exposure. The capability of rapidly scanning a large gene in a large number of samples for the presence and location of all heterozygous mutations and gene variations can result in critical improvements in health care. To achieve this AndCare will develop the method proved feasible in Phase I into a new diagnostic product for the rapid, quantitative, electrochemical detection of altered nucleic acid sequences. In Phase II AndCare will exploit innovative methodology to electrochemically detect inherent differences in melting temperatures of homologous and mismatched DNA annealed to an array of specific probes of wild-type sequence. In this way specific heterozygous and homozygous mutations present in a given patient sample are detected. The expected result is an assay capable of detecting point mutations as well as small insertion or deletion mutations. The technology is well suited for automation and high-throughput genetic diagnostics in clinical and research laboratories. Dr. Henkens and his staff have pioneered the use of screen-printed, disposable, amperometric sensors using colloidal gold electrodes for use with electrochemical monitors. This technology is the platform that will be used in this project. PROPOSED COMMERCIAL APPLICATION: Tools developed in this project provide new opportunities to understand the genetic basis for individual differences in susceptibility to disease. We believe that the capability of rapidly testing a large gene in a large number of samples for the presence and location of all heterozygous mutations and gene variations has important commercial applications in research and clinical laboratories.